Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels
(2017) In Science Signaling 10(487).- Abstract
The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier,... (More)
The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin (Ctnnb1). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors (Foxf2, Foxl2, Foxq1, Lef1, Ppard, Zfp551, and Zic3) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of Foxf2, Foxq1, Ppard, or Zic3 transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models.
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- author
- Hupe, Mike ; Li, Minerva Xueting LU ; Kneitz, Susanne ; Davydova, Daria ; Yokota, Chika ; Kele, Julianna ; Hot, Belma ; Stenman, Jan M LU and Gessler, Manfred
- publishing date
- 2017-07-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Brain/cytology, Embryo, Mammalian/cytology, Embryonic Development/physiology, Endothelial Cells/cytology, Gene Expression Profiling, Gene Expression Regulation, Developmental/physiology, Mice, Mice, Transgenic
- in
- Science Signaling
- volume
- 10
- issue
- 487
- pages
- 12 pages
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- pmid:28698213
- scopus:85024855472
- ISSN
- 1937-9145
- language
- English
- LU publication?
- no
- id
- ff76c529-123e-4df2-839c-6eaf5925cf98
- alternative location
- https://stke-sciencemag-org.ludwig.lub.lu.se/content/10/487/eaag2476.abstract
- date added to LUP
- 2021-08-09 12:56:28
- date last changed
- 2024-04-20 09:24:57
@article{ff76c529-123e-4df2-839c-6eaf5925cf98,
abstract = {{<p>The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin (Ctnnb1). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors (Foxf2, Foxl2, Foxq1, Lef1, Ppard, Zfp551, and Zic3) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of Foxf2, Foxq1, Ppard, or Zic3 transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models.</p>}},
author = {{Hupe, Mike and Li, Minerva Xueting and Kneitz, Susanne and Davydova, Daria and Yokota, Chika and Kele, Julianna and Hot, Belma and Stenman, Jan M and Gessler, Manfred}},
issn = {{1937-9145}},
keywords = {{Animals; Brain/cytology; Embryo, Mammalian/cytology; Embryonic Development/physiology; Endothelial Cells/cytology; Gene Expression Profiling; Gene Expression Regulation, Developmental/physiology; Mice; Mice, Transgenic}},
language = {{eng}},
month = {{07}},
number = {{487}},
publisher = {{American Association for the Advancement of Science (AAAS)}},
series = {{Science Signaling}},
title = {{Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels}},
url = {{https://stke-sciencemag-org.ludwig.lub.lu.se/content/10/487/eaag2476.abstract}},
volume = {{10}},
year = {{2017}},
}